Mutation of the p53 tumor suppressor gene in transitional cell carcinoma of the urinary tract in Taiwan.

Early detection of a mutated p53 gene is thought to provide useful information in a wide range of human tumors. The aim of this study was to identify the role of the p53 gene in transitional cell carcinoma of the urinary tract. From March 1992 to July 2003, 75 patients (54 men and 21 women) with a mean age of 66.85 years and pathologically diagnosed transitional cell carcinoma were enrolled in this study. Fifty-eight patients had bladder cancer, eight had ureteral cancer, and nine had renal-pelvic cancer. Rapid screening for mutation of the p53 gene was performed using polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and sequencing analysis. Primer sets were designed to amplify fragments within exons 4, 5, 6, 7, and 8 of the p53 gene. Pathology classified 37 tumors as low grade and 38 as high grade. Tumor stage was pT1 or less in 29 patients and at least pT2 in 46 patients. Of the 75 patients in this study, 47 (62.7%) had a p53 mutation. Of the patients with a p53 mutation, 33 (70.2%) had invasive tumors. Invasive tumors were associated with p53 mutation (p < 0.05). Noted in 20 patients (26.7%), exon 4 was the most common site of the mutation. Of the patients with exon 4 mutations, 15 (75%) had invasive tumors and nine (45%) had high-grade tumors. Additionally, among the 20 patients with a common polymorphism at codon 72, 16 (80%) had invasive tumors and 14 (70%) had high-grade tumors. In this study, 62.7% of patients with transitional cell carcinoma had a p53 mutation, suggesting that the p53 gene mutation may be used as a marker of transitional cell carcinoma. Invasive tumors are more likely to have a p53 gene mutation. A simple analysis of the p53 gene using PCR/SSCP is suitable for screening for p53 abnormalities in transitional cell carcinoma. The relationship between cancer risk and the codon 72 polymorphism of exon 4 needs further investigation.